1. Field of Invention
This invention relates to a novel process for the synthesis of 2,3-dimethoxy-5-methyl-6-substituted-1,4-benzoquinones having the formula (I): ##STR3## wherein R is a group of the formula ##STR4## in which s is an integer of from 0 to 11, and A and B are hydrogen or A-B forms a direct bond.
Compounds of formula (I) are known as coenzymes Q, and especially, a compound of formula (I) in which A-B forms a direct bond and s is 9, namely 2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone [2,3-dimethoxy-5-methyl-6-(3,7,11,15,19,23,27,31,35,39-decamethyl-tetracon tadecaen-2,6,10,14,18,22,26,30,34,38,-yl)-1,4-benzoquinone], is called coenzyme Q.sub.10 and is expected to show various clinical effects from the medicinal and pharmacological viewpoints because it participates in the electron transport system in living bodies and plays an important role in producing energies.
2. Description of Prior Arts
As the process for the synthesis of a series of quinone compounds represented by this coenzyme Q.sub.10, there is known a process comprising reacting 2,3-dimethoxy-5-methyl-1,4-benzohydroquinone or its 1-monoacylate with (iso)decaprenol or its reactive derivative in the presence of an acidic condensation catalyst such as a protonic acid, e.g., formic acid, sulfuric acid, hydrochloric acid, phosphoric acid or p-toluenesulfonic acid, a Lewis acid, e.g., zinc chloride, aluminum chloride or a boron trifluoride-ether complex, or a mixture thereof, and if required hydrolyzing the condensation product, and oxidizing it to form the intended compound (see Japanese Pat. Publications No. 17513/64, No. 17514/64 and No. 3967/71).
In this known process, however, since the yield at the condensation step is not high, the yield of the intended quinone compound is 30% at the highest even when calculated as the crude product. Further, each of the acid catalysts used has a high corrosive property and has bad influences on equipment, and the metals dissolved out of the catalysts contaminate the products. Accordingly, this process is disadvantageous from the industrial viewpoint.
Moreover, since an acid catalyst as mentioned above should be used in the above known process, such operations as neutralization and extraction are required for separating the intended compound from the reaction mixture. Still further, a large quantity of the catalyst should naturally be used as compared with the amount of the starting reactants, and such catalyst should be discarded after completion of the reaction. Therefore, this known process is disadvantageous because the manufacturing cost is increased and the discarded catalyst causes environmental pollution. As is seen from the foregoing, this known process involves various industrial difficulties and disadvantages.
Various attempts have heretofore been made to improve the yield at the condensation step, and there has been developed a process in which 2,3-dimethoxy-5-methyl-6-halogeno-1,4-benzohydroquinone 1,4-dimethoxy-methyl ethers or 1,4-diacetates are linked with .pi.-allyl type nickel complexes represented by the following chemical formula: ##STR5## wherein x is halogen, R is as defined above, denotes a semi-bond, and denotes a double bond,
and corresponding benzohydroquinones are obtained in high yields (see Japanese Patent Application Laid-Open Specifications No. 25137/72 and No. 85546/73). In this process, the yield at the condensation step can be highly improved, but since Ni(CO).sub.4 used for preparation of .pi.-allyl type nickel complexes has a toxic activity to the respiratory organs and it is a gaseous substance and its handling is troublesome, it is very difficult to industrialize this process.